Publikationen

Molecular switches are the fundamental building blocks in the field of synthetic biology. The majority of these switches is based on protein-protein, protein-DNA or protein-RNA interactions that are responsive towards endogenous metabolites or external stimuli like small molecules or light. By the rational and predictive reassembling of multiple compatible molecular switches, complex synthetic signaling networks can be engineered. Here we review how these switches were used for the regulation of important cellular processes at every level of the signaling cascade. In the second part we review how these switches can be assembled to open- and closed-loop control signaling networks and how these networks can be applied to facilitate cattle reproduction, to treat diabetes or to autonomously detect and cure disease states like gouty arthritis or cancer. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

TSynthetic biology aims at the rational design and construction of devices, systems and organisms with desired functionality based on modular well-characterized biological building blocks. Based on first proof-of-concept studies in bacteria a decade ago, synthetic biology strategies have rapidly entered mammalian cell technology providing novel therapeutic solutions. Here we review how biological building blocks can be rewired to interactive regulatory genetic networks in mammalian cells and how these networks can be transformed into open- and closed-loop control configurations for autonomously managing disease phenotypes. In the second part of this tutorial review we describe how the regulatory biological sensors and switches can be transferred from mammalian cell synthetic biology to materials sciences in order to develop interactive biohybrid materials with similar (therapeutic) functionality as their synthetic biological archetypes. We develop a perspective of how the convergence of synthetic biology with materials sciences might contribute to the development of truly interactive and adaptive materials for autonomous operation in a complex environment. 2012 © The Royal Society of Chemistry.

Modularly structured signaling networks coordinate the fate and function of complex biological systems. Each component in the network performs a discrete computational operation, but when connected to each other intricate functionality emerges. Here we study such an architecture by connecting auxin signaling modules and inducible protein biotinylation systems with transcriptional control systems to construct synthetic mammalian high-detect, low-detect and band-detect networks that translate overlapping gradients of inducer molecules into distinct gene expression patterns. Guided by a mathematical model we apply fundamental computational operations like conjunction or addition to rewire individual building blocks to qualitatively and quantitatively program the way the overall network interprets graded input signals. The design principles described in this study might serve as a conceptual blueprint for the development of next-generation mammalian synthetic gene networks in fundamental and translational research. © 2012 The Royal Society of Chemistry.

The rapidly emerging ability to design and construct synthetic gene networks in mammalian cells is based on the availability of mutually compatible genetic switches that enable the time-dependent induction of transgene expression in response to the dose of an externally applied stimulus. As these genetic switches are inherently compatible with mammalian cell physiology, they are as well predestined to control the functionality of cell-free synthetic devices within an overall physiologic background. In this chapter, we describe how a genetic switch that was originally designed for gene therapeutic studies can be applied in materials science to design and construct a biohybrid hydrogel that can be used to release a therapeutic growth factor in response to an externally applied stimulus for controlling cell fate and function in a time- and space-resolved manner. © 2012 Springer Science+Business Media, LLC.

The field of synthetic biology is rapidly expanding and has over the past years evolved from the development of simple gene networks to complex treatment-oriented circuits. The reprogramming of cell fate with open-loop or closed-loop synthetic control circuits along with biologically implemented logical functions have fostered applications spanning over a wide range of disciplines, including artificial insemination, personalized medicine and the treatment of cancer and metabolic disorders. In this review we describe several applications of interactive gene networks, a synthetic biology-based approach for future gene therapy, as well as the utilization of synthetic gene circuits as blueprints for the design of stimuli-responsive biohybrid materials. The recent progress in synthetic biology, including the rewiring of biosensing devices with the body's endogenous network as well as novel therapeutic approaches originating from interdisciplinary work, generates numerous opportunities for future biomedical applications. © 2012 Elsevier Ltd.

Advances in the development of molecular tools for the inducible control of transcription, translation, and protein degradation are the basis for the rapidly emerging design and construction of synthetic gene networks in mammalian cells. In this chapter, we describe such tools and how they can be integrated into a synthetic gene network with desired functionality. The network design and construction process is illustrated in the form of a detailed protocol for the implementation of a logic NOR gate based on an inducible promoter combined with an inducible protein degradation system. © 2012 Springer Science+Business Media, LLC.

Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications. © 2011 Macmillan Publishers Limited. All rights reserved.

The recent implementation of various high-throughput biochemical and bioanalytical platforms for the study of biological systems has resulted in a wealth of experimental information that systems biology integrates into models and functional descriptions of organisms. The fast tempo of systems biology development is currently bringing in a revolution in the understanding of cell networks by providing with a holistic comprehension of cellular components and their interaction dynamics. This thorough description of biological systems has laid the grounds for the development of synthetic biology, a discipline applying basic principles of engineering for the rational assembly of biological modules into higher order complex biological systems with desired properties. Despite the success of this new field for the generation of biotechnological tools, it has not been yet widely applied to plant systems. This review aims at describing the current status of systems biology, its contribution to our understanding of plant metabolism, expression and regulatory networks and how synthetic biology approaches could benefit utilising plant and bacterial 'omics' as a source for the design and development of biological modules for the improvement of plant stress tolerance and crop production, among other applications. The article further describes synthetic biology strategies currently being applied to plant metabolic engineering, development of signalling pathways and synthetic organelles, and the potential of this new field for the understanding of plant cellular functioning and the generation of plant biotechnological tools. © 2012 Elsevier B.V..

The protective capabilities of sol-gel coatings are determined by their physical barrier properties. For an effective protection, a homogenous crack-free material is required, which prevents from attacks of corrosive species. When the coating is damaged, active corrosion protection is usually achieved by the use of inhibitors. Among the different inhibitors rare earth ions and especially cerium have shown effective inhibiting properties. Due to the complexity of the corrosion processes, a combination of inhibitors is expected to be superior to a monocomponent inhibiting. The aim of this study was to prove which other ions, used in combination with cerium, can improve the corrosion protection abilities of hybrid silica based inorganic-organic sol-gel coatings applied on aluminium alloy 2024 substrates. Mixtures of cerium nitrate with two other potential inhibitor substances were incorporated into a sol-gel matrix and their behaviour in neutral salt spray test and during EIS measurements was investigated. The Ce–P–Pr inhibitor combination (Ce3+, PO43−, Pr3+) has shown the best long-term corrosion protection properties at low doping levels.

In recent years, many hybrid inorganic-organic systems have been proposed in order to replace the traditional conversion coatings on metals like aluminum, and some results have been promising. However, many proposed solutions are based on complicated processes which are not easy to be adapted to industrial scale. The aim of this study was to establish a simple process leading to the production of highly efficient corrosion protective hybrid sol-gel coating systems for the aluminum alloys as replacement for the highly hazardous conventional chromate conversion coatings. Hybrid coatings have been realized by means of the sol-gel process. CeO2 and ZnO have been introduced as dispersions of nanoparticles in the system and used as corrosion inhibitors. The aim of this work was to obtain pore-free coatings with increased barrier properties using nanoparticles that possess the double function of pore fillers and corrosion inhibitors. The proposed processes led to coating materials with good adherence to the aluminum substrate and an extremely long life in the accelerated neutral salt spray test according to DIN ISO 9227. Electrochemical impedance spectroscopy approves these results by high impedance values in the low-frequency region of the Bode plot.